Long COVID trajectories in the prospectively followed RECOVER-Adult US cohort, 2025, Thaweethai et al.

[Chandelier]

Long COVID trajectories in the prospectively followed RECOVER-Adult US cohort

Abstract​

Longitudinal trajectories of Long COVID remain ill-defined, yet are critically needed to advance clinical trials, patient care, and public health initiatives for millions of individuals with this condition.

Long COVID trajectories were determined prospectively among 3,659 participants (69% female; 99.6% Omicron era) in the National Institutes of Health Researching COVID to Enhance Recovery (RECOVER) Adult Cohort.
Finite mixture modeling was used to identify distinct longitudinal profiles based on a Long COVID research index measured 3 to 15 months after infection.
Eight longitudinal profiles were identified.
Overall, 195 (5%) had persistently high Long COVID symptom burden, 443 (12%) had non-resolving, intermittently high symptom burden, and 526 (14%) did not meet criteria for Long COVID at 3 months but had increasing symptoms by 15 months, suggestive of distinct pathophysiologic features.
At 3 months, 377 (10%) met the research index threshold for Long COVID.
Of these, 175 (46%) had persistent Long COVID, 132 (35%) had moderate symptoms, and 70 (19%) appeared to recover.

Identification of these Long COVID symptom trajectories is critically important for targeting enrollment for future studies of pathophysiologic mechanisms, preventive strategies, clinical trials and treatments.

Spoiler: Authors

Thaweethai, Tanayott; Donohue, Sarah E.; Martin, Jeffrey N.; Hornig, Mady; Mosier, Jarrod M.; Shinnick, Daniel J.; Ashktorab, Hassan; Atieh, Ornina; Blomkalns, Andra; Brim, Hassan; Chen, Yu; Cortez, Melissa M.; Erdmann, Nathan B.; Flaherman, Valerie; Goepfert, Paul; Goldman, Jason D.; Hamburg, Naomi M.; Han, Jenny E.; Heath, James R.; Jacoby, Vanessa; Jolley, Sarah E.; Kelly, J. Daniel; Kelly, Sara W.; Kim, C.; Krishnan, Jerry A.; Letts, Rebecca; Levitan, Emily B.; Modes, Matthew E.; McComsey, Grace A.; Metz, Torri D.; Mullington, Janet M.; Ofotokun, Igho; Okumura, Megumi J.; Paredes, Claudia Castillo; Patterson, Thomas F.; Peluso, Michael J.; Reece, Rebecca; Sherif, Zaki A.; Simhan, Hyagriv N.; Simmons, Christopher; Singh, Upinder; Taylor, Barbara S.; Taylor, Brittany D.; Trinity, Joel D.; Troxel, Andrea B.; Utz, Paul J.; Vasey, Andrew J.; Weinberger, Elisheva; Wiley, Zanthia; Wisnivesky, Juan; Yee, Lynn M.; Horwitz, Leora; Foulkes, Andrea S.; Levy, Bruce D.

Web | DOI | PDF | Nature Communications

 

[rvallee]

This seems short (15 months) and small. RECOVER was supposed to have huge cohorts.

Anyway, it confirms what has been known since late 2020. Is this going to be enough? If not what is?

As usual it makes a total mockery of all the fake rehab that has been asserted to work. It's been obvious for many years that fluctuations are chaotic and include the kind of chance natural improvements that make all boasts about rehab so weak that they deserve to be called fraudulent. Any treatment of homeopathy or whatever would produce similar results.

They also feature quite a lot of delayed worsening, making any claims of permanent recovery completely inappropriate. No one can know for sure either way.

Female preponderance not as extreme as most studies:

Participants with persistent, high symptom burden (profile A) compared to participants with consistent, minimal to no symptom burden (profile H) were more often female (77 vs. 64%)

It's easy to bullshit in thirds, and while it's close enough, it's also not that:

Among the 10% of participants who met research index criteria for Long COVID at 3 months, 46% were in the persistent Long COVID group, 35% continued to have intermittent Long COVID-related symptoms, and 19% were in the group that was improving over time.

 

[Dolphin]

Study reveals insights into long COVID trajectories in adults

Millions of patients have developed long COVID, a chronic condition that involves a range of symptoms, including fatigue, brain fog, dizziness, and palpitations that persist for at least three months after SARS-CoV-2 infection. In a new analysis of adult participants in the NIH funded...

www.eurekalert.org

News Release 17-Nov-2025

Study reveals insights into long COVID trajectories in adults​

New research led by Mass General Brigham followed more than 3,500 patients, finding that 10.3% had symptoms consistent with long COVID three months after infection, 81% of whom continued to experience persistent or intermittent symptoms a year later

Peer-Reviewed Publication
Brigham and Women's Hospital


New research led by Mass General Brigham followed more than 3,500 patients, finding that 10.3% had symptoms consistent with long COVID three months after infection, 81% of whom continued to experience persistent or intermittent symptoms a year later

Millions of patients have developed long COVID, a chronic condition that involves a range of symptoms, including fatigue, brain fog, dizziness, and palpitations that persist for at least three months after SARS-CoV-2 infection. In a new analysis of adult participants in the NIH funded Researching COVID to Enhance Recovery (RECOVER) Initiative, Mass General Brigham researchers identified eight different trajectories that long COVID can take, depending on severity, duration, and whether symptoms improve or worsen. Their findings are published in Nature Communications.

“This study addresses an urgent need to define the differing long COVID trajectories,” said senior author Bruce Levy, MD, of the Mass General Brigham Department of Medicine and the Division of Pulmonary and Critical Care Medicine. “Our findings will help determine what resources are needed for clinical and public health support of individuals with long COVID and will also inform efforts to understand long COVID’s biological basis.”

To identify long COVID trajectories, the researchers followed 3,659 adult RECOVER participants who first contracted SARS-CoV-2 during the Omicron variant era (after Dec. 1, 2021). The participants completed a comprehensive symptom questionnaire at 3-, 6-, 9-, 12-, and 15-months post-infection to track changes over time. Then, the researchers identified patients with long COVID using the long COVID research index, a symptom-based tool that was previously developed by Mass General Brigham researchers.

Overall, 10.3% of patients had long COVID symptoms three months after infection, and 81% of these patients continued to experience persistent or intermittent symptoms a year later. Female patients and those who had been hospitalized with an acute SARS-CoV-2 infection were more likely to develop persistently severe long COVID symptoms.

The researchers identified eight different long COVID trajectories. Some of these trajectories included persistently severe symptoms, intermittently severe symptoms, gradually improving symptoms, gradually worsening symptoms, and mild symptoms that only appeared after 15 months.

“The variability we identified will enable future studies to evaluate risk factors and biomarkers that could explain why patients vary in time of recovery, and help identify potential therapeutic targets,” said first author Tanayott Thaweethai, PhD, assistant professor at Massachusetts General Hospital Biostatistics.

Authorship: In addition to Levy and Thaweethai, Mass General Brigham authors include Andrea S. Foulkes (co-senior author), and Daniel J. Shinnick. Additional authors include Sarah E. Donohue, Jeffrey N. Martin, Mady Hornig, Jarrod M. Mosier, Hassan Ashktorab, Ornina Atieh, Andra Blomkalns, Hassan Brim, Yu Chen, Melissa M. Cortez, Nathan B. Erdmann, Valerie Flaherman, Paul Goepfert, Jason D. Goldman, Naomi M. Hamburg, Jenny E. Han, James R. Heath, Vanessa Jacoby, Sarah E. Jolley, J. Daniel Kelly, Sara W. Kelly, C. Kim, Jerry A. Krishnan, Rebecca Letts, Emily B. Levitan, Matthew E. Modes, Grace A. McComsey, Torri D. Metz, Janet M. Mullington, Igho Ofotokun, Megumi J. Okumura, Claudia Castillo Paredes, Thomas F. Patterson, Michael Peluso, Rebecca Reece, Zaki A. Sherif, Hyagriv N. Simhan, Christopher Simmons, Upinder Singh, Barbara S. Taylor, Brittany D. Taylor, Joel D. Trinity, Andrea B. Troxel, Paul J. Utz, Andrew J. Vasey, Elisheva Weinberger, Zanthia Wiley, Juan Wisnivesky, and Lynn M. Yee, and Leora Horwitz on behalf of the RECOVER Adult Cohort.

Disclosures: A full list of disclosures can be found in the paper.

Funding: This research was funded by the National Institutes of Health (OTA OT2HL161841, OT2HL161847, OT2HL156812, and OT2HL162087) as part of RECOVER. Additional support for T.T., A.S.F., and B.D.L. was provided by grant R01 HL162373.

Paper cited: Thaweethai, T et al. “Long COVID trajectories in prospectively followed RECOVER Adult participants” Nature Communications DOI: 10.1038/s41467-025-65239-4

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About Mass General Brigham
Mass General Brigham is an integrated academic health care system, uniting great minds to solve the hardest problems in medicine for our communities and the world. Mass General Brigham connects a full continuum of care across a system of academic medical centers, community and specialty hospitals, a health insurance plan, physician networks, community health centers, home care, and long-term care services. Mass General Brigham is a nonprofit organization committed to patient care, research, teaching, and service to the community. In addition, Mass General Brigham is one of the nation’s leading biomedical research organizations with several Harvard Medical School teaching hospitals. For more information, please visit massgeneralbrigham.org.

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Journal​

Nature Communications

DOI​

10.1038/s41467-025-65239-4

Method of Research​

Data/statistical analysis

Subject of Research​

People

Article Title​

Long COVID trajectories in prospectively followed RECOVER Adult participants

Article Publication Date​

17-Nov-2025

COI Statement​

A full list of disclosures can be found in the paper.

 

[Yann04]

It’s notable that as for the overall incidence new cases were in large part making up for the recoveries.